O-2-SENSITIVE K-DERIVED SMALL-CELL CARCINOMA-CELLS OF THE HUMAN LUNG(CHANNELS IN NEUROEPITHELIAL BODY)

Neuroepithelial bodies act as airway O-2 sensors, but studies of their activity at the cellular level have been severely limited because the y are present at such a low density in lung tissue. Small cell lung ca rcinoma (SCLC) cells are believed to be derived from neuroepithelial b ody cells and may represent a model system for investigating the mecha nisms of airway chemoreception. Here we have used the whole cell patch -clamp technique to investigate the effects of acute hypoxia on voltag e-gated, ionic currents and membrane potential in H-146 SCLC cells. St ep depolarizations evoked transient inward currents due to activation of Na+ and Ca2+ channels, followed by outward K+ currents. K+ currents were partially inhibited by 200 mu M Cd2+ (indicative of the presence of a Ca2+-dependent component of the K+ current) and were inhibited b y tetraethylammonium (TEA) in a concentration-dependent manner, althou gh even at 100 mM TEA, a residual K+ current could be detected. Hypoxi a (PO2 15-20 mmHg) caused a reversible inhibition of outward K+ curren ts without affecting inward currents. Inhibition by hypoxia was also o bserved in the presence of Cd2+. Hypoxia and TEA caused membrane depol arization in H-146 cells, and their effects appeared additive. These f indings indicate that H-146 cells possess O-2-sensitive, Ca2+-independ ent K+ channels that can influence cell membrane potential. SCLC cells may, therefore, represent a good model for investigating the mechanis ms underlying O-2 sensing by airway chemoreceptor cells.